REGULATION-LYMPHOKINE PRODUCTION BY HUMAN T LYMPHOCYTES

调节 - 人类 T 淋巴细胞产生淋巴细胞因子

基本信息

批准号：
3135287
负责人：
MICHAEL J PARMELY
金额：
$ 9.98万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-12-01 至 1990-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3135287
关键词：
B lymphocyte Pseudomonas aeruginosa T lymphocyte cell differentiation clone cells colony stimulating factor human tissue immunochemistry immunoregulation interferons interleukin 2 laboratory mouse leukocyte activation /transformation lymphokines microorganism immunology peptidases tissue /cell culture

项目摘要

Thymus-derived lymphocytes serve as the principal cellular regulators of immune responses communicating with other cell types via soluble mediators called lymphokines. Activation of T cells is accompanied by lymphokine release but cells differ both in the range of mediators they can produce and the activation signals capable of eliciting their production. Our purpose is to elucidate both extrinsic and intrinsic regulation of lymphokine release. A model system using a large panel of well-characterized human T lymphocyte clones will be employed to test the hypothesis that the nature of the antigenic signal delivered to a heterogeneous population of cells determines, in part, the type of lymphokines produced and that T cells committed to different antigenic determinants also differ in the lymphokines they are capable of secreting. Mediators regulating myelopoietic progenitor cell (colony stimulating factor), B cell (B cell growth factor), T cell (interleukin-2) and macrophage (interferon-gamma) growth and differentiation will be studied. As a means of identifying the inter- and intracellular signals required for lymphokine release, interferon-gamma (IFN-gamma) production by cloned human T cells will serve as a model. IFN-gamma production is selectively inhibited by certain bacterial products. Thus, determining the mechanism by which these factors suppress IFN-gamma release should yield valuable information on the signals leading to lymphokine production by T cells. Of particular interest will be accessory cell and interleukin requirements and intracellular messengers (e.g., calcium mobilization and protein phosphorylation). Results of these studies should not only provide valuable information on the activation signals required for lymphokine production by T cells, but should also suggest means of controlling T cell functions by pharmacologic or immunologic intervention (e.g., appropriate construction of synthetic vaccines). Since IFN-gamma, in particular, is known to be a potent activator of macrophages and natural killer cells, both of which are important in limiting tumor growth and metastases, information derived from this project will have direct relevance to anti-tumor immunity.

胸腺来源的淋巴细胞是主要细胞调节剂通过可溶性介体与其他细胞类型通信的免疫反应称为淋巴细胞。 T细胞的激活伴随着淋巴因子释放，但细胞在可以产生的介体的范围内有所不同以及能够引起其生产的激活信号。我们的目的是阐明外在和内在调节的淋巴因子释放。使用大型面板的模型系统特征良好的人类T淋巴细胞克隆将被用来测试假设抗原信号的性质传递到A 细胞的异质种群部分决定了产生的淋巴因子，并表明将T细胞用于不同的抗原决定因素在它们能够分泌的淋巴细胞方面也有所不同。调节骨髓祖细胞细胞的介质（刺激菌落因子），B细胞（B细胞生长因子），T细胞（白介素2）和将研究巨噬细胞（干扰素 - γ）生长和分化。作为识别所需的细胞间和细胞内信号的手段克隆人的淋巴因子释放，干扰素伽马（IFN-gamma）生产 T细胞将用作模型。 IFN-Gamma的产生有选择性被某些细菌产品抑制。因此，确定机制这些因素抑制IFN-gamma释放应产生有价值的有关导致T细胞淋巴因子产生的信号的信息。的特别感兴趣的是附件和白介素的要求以及细胞内信使（例如钙动员和蛋白质磷酸化）。这些研究的结果不仅应提供有关淋巴因子所需的激活信号的宝贵信息通过T细胞生产，但也应提出控制T细胞的手段通过药理学或免疫学干预的功能（例如，适当合成疫苗的结构）。由于尤其是IFN-Gamma，已知是巨噬细胞和天然杀伤细胞的有效激活因子，这两者在限制肿瘤生长和转移酶中很重要，从该项目得出的信息将与抗肿瘤免疫。